A diagnostic technique of using a biochip is attracting attention in advanced medical fields such as tailor-made medical practice and early diagnosis. The biochip generically designates devices carrying, as a capturing molecule, a biomolecule or a bioactive substance, such as antigen, antibody, DNA, RNA, sugar, polysaccharide, ligand, receptor, peptide, or chemical substance, arrayed and immobilized on a substrate.
A typical example of the biochip is a DNA chip. The DNA chip is aimed at detecting and quantifying a gene by allowing a DNA immobilized on a substrate to react with an analyte DNA or RNA and thus, detecting the fluorescence label introduced to the analyte DNA or RNA.
However, biochips including the DNA chip are lower for the reproducibility of the data obtained because of easier photobleaching (color-fading) of the dye used for fluorescence labeling. Therefore, there is a problem that the data obtained is still unsatisfactory in reliability for clinical applications.
Semiconductor nanoparticles such as CdSe have been known as fluorescent dyes resistant to the photobleaching. However, such semiconductor nanoparticles show fluorescence characteristics significantly different from those of the dye widely used for DNA chips currently such as Cy3 and Cy5, and thus it is difficult to apply such nanoparticles to the DNA chip analyzers currently used widely. In addition, when an analyte DNA is fluorescent-labelled or a DNA on a substrate is hybridized, it is difficult to remove semiconductor nanoparticles which have not labelled the analyte DNA fluorescently or semiconductor nanoparticle-labelled DNAs which have not been hybridized with the analyte DNA.
Thus, there are still these problems remaining in applying semiconductor nanoparticles to DNA chips.
Fluorescence silica particles containing an organic dye inside a silica particle are reported as a method of stabilizing the organic dye (see, for example, Non-patent Documents 1 to 3).
However, fluorescence silica particles so far reported, which had a particle diameter of at least approximately 30 nm. Therefore, there are problems that they did not allow efficient fluorescence labelling for use as a DNA chip dye, gave insufficient fluorescent intensity because of low integration of the fluorescent dye, and were vulnerable to photobleaching.
Non-patent Document 1: J. Phys. Chem. B 1999, 703, 1408-1415
Non-patent Document 2: Nano Letters 2005, 5, 113
Non-patent Document 3: Nano Letters 2005, 5, 37